In this chapter

“This integration of addiction and HIV treatment provides an opportunity to coordinate care of these 2 medical conditions in 1 setting, the HIV primary care clinic.”48

Buprenorphine and the National HIV/AIDS Strategy

Two important components of HIV prevention are addressing transmission risk behaviors and improving adherence to ARVs. The integration of buprenorphine into HIV primary care settings achieves both of these goals—and the goals of the National HIV/AIDS Strategy. In fact, informing the greater HIV community about the feasibility and effectiveness of buprenorphine is an important component of the U.S. Department of Health and Human Services’ National HIV/AIDS Strategy Federal Operational Plan.

The Ryan White HIV/AIDS Program has led the way in creating comprehensive wraparound services and spearheading the notion of a medical home. The integration of substance abuse treatment within a Ryan White-fundedclinic expands on this commitment and offers new hope.

"Developing effective integrated care models for complex patient populations, like HIV-infected drug users, is important for several reasons:

Third, data from randomized controlled trials have suggested that integrating services at a single site may improve both medical and substance abuse treatment outcomes."49

Many integrated service programs provide public HIV primary care. As these sites—whether HIV specialty or community health clinics—are already attending to a host of health issues in their patients, including HIV, and given the high prevalence of HIV and opioid dependence, including buprenorphine in the medical home model makes sense. It allows patients with chaotic lives to readily access services under one roof and providers to treat addiction as a chronic medical condition while addressing additional medical needs.

It also enables patients who have forged trusting and communicative relationships with their HIV primary care doctor to continue that relationship in the context of culturally competent care and now, to address their opioid dependence. Medication adherence and health outcomes are also optimized when HIV primary care is linked with substance abuse treatment.50

This work is made possible thanks to the passage of the Drug Addiction Treatment Act of 2000, otherwise known as DATA 2000.

Buprenorphine

What Is Buprenorphine?

Buprenorphine is a semisynthetic opioid.36 Subutex is a white, oval tablet that contains only buprenorphine (and was discontinued as of January 1, 2012, by the original manufacturer, Reckitt Benckiser, although it is available generically).51 A coformulated version of buprenorphine and naloxone is called Suboxone. In tablet form, it’s an orange, hexagonal pill with buprenorphine and naloxone in a 4:1 ratio.36,52 (As of 2010, Suboxone is also available as a sublingual film.) Whether as a film or tablet, buprenorphine opioid treatment is taken sublingually, meaning under the tongue.

There’s an important distinction between Subutex and Suboxone: Suboxone is meant to discourage diversion as naloxone binds to—and blocks—opioid receptors.36 By itself, naloxone is injected to reverse overdose. But when taken sublingually with buprenorphine, naloxone has no effect. This is because sublingual naloxone is not as well absorbed. Naloxone was added to buprenorphine to block the effects of heroin and other opioids—something it does very successfully.53 If Suboxone is injected in an attempt to get high, it can initiate immediate withdrawal (otherwise known as “precipitated withdrawal”) in individuals who are on other opioids.38 Because naloxone discourages use by injection, it makes Suboxone diversion less likely than methadone or Subutex (buprenorphine alone).54–57 (To read more about this, see How Do I Identify Precipitated Withdrawal, and What Is It? in Chapter 5.)

As of 2012, manufacturer Reckitt Benckiser has suspended Subutex, stating that monotherapy of buprenophine (without naloxone) increases diversion and misuse.

DATA 2000

The Drug Addiction Treatment Act of 2000 (DATA 2000) is the seminal legislation that made office-based treatment of opioid addiction possible. More specifically, it enabled qualifying physicians outside of opioid treatment programs (i.e., methadone clinics) to prescribe and/or dispense Schedule III, IV, and V opioid medications approved by the U.S. Food and Drug Administration (FDA). Buprenorphine is considered a Schedule III narcotic.

“The promise of DATA 2000 is to help destigmatize opioid addiction treatment and to enable qualified physicians to manage opioid addiction in their own practices.”

On October 8, 2002, the FDA approved two sublingual formulations: Subutex® (buprenorphine) and Suboxone® (buprenorphine/naloxone) tablets for the treatment of opioid addiction. (See “Getting Started” to learn more.)

Together, these milestones paved the way for SPNS Buprenorphine Initiative grantees to prescribe Suboxone within their HIV primary care settings and thus created ever more comprehensive wraparound services for their patients.

On August 31, 2010, the FDA added another treatment option for addressing opioid abuse—Suboxone sublingual film. The film is administered similarly to Suboxone tablets; however, it dissolves more quickly under the tongue for speedier administration effectiveness. Additionally, Naltrexone, an extended-release injectable form of opioid treatment, is now available.

Though released after the conclusion of the Buprenorphine Initiative, these approvals extend the groundbreaking work first set forth in DATA 2000.

What Does It Do?

Buprenorphine stabilizes brain neurochemistry38 because it displaces other opioids from their receptors and then occupies the same receptors, thus preventing withdrawal symptoms.54

Because buprenorphine is a partial opioid agonist, it does not stimulate the same degree of activity at the brain's opioid receptors as full opioid agonists do (e.g., heroin, morphine, OxyContin, fentanyl, and methadone). As a result, people using buprenorphine may still experience euphoria and become physically dependent, but to a lesser extent than with full agonists.36

If patients use other opioids while already on Suboxone, buprenorphine will block the euphoria and other effects produced by opioids.38 Providers have cited how lucid their patients are on buprenorphine and how dramatically it has improved their daily functioning.54

Is Buprenorphine Addictive?

Buprenorphine does carry some risk for psychological and physical dependence,58 although potential for addiction is considered generally low, certainly a lesser degree than full opioid agonists, and it seems easier to discontinue than methadone.53,59 That buprenorphine treatment may be easier to discontinue than methadone does not necessarily mean one medication-assisted addiction treatment measure is superior to another.60 All patients should be screened to see which treatment option may be best suited for them. If patients choose to stop using buprenorphine, they should be tapered off slowly to decrease risk of withdrawal symptoms and relapse to opioid use.

What Are Agonists and Antagonists and How Do They Relate to Buprenorphine?

Buprenorphine is considered a partial agonist--partial antagonist medication, meaning that it works by both activating and blocking opioid receptors.55 The antagonist (or blocking) property provides a "ceiling effect" on buprenorphine's ability to control pain and induce euphoria. Up to a certain dose, buprenorphine's agonist (or activating) property predominates, and each dose increase is accompanied by an increase in the intensity of the drug's analgesic and euphoric effects. Beyond a ceiling dose, however, the antagonist property of buprenorphine predominates. At that point, the effects of the drug level off and cannot be further enhanced--even with additional buprenorphine.54

By contrast, heroin and methadone are full agonists: They have purely activating effects on opioid receptors and therefore lack buprenorphine's ceiling effect. As a result, methadone is effective for addicts who require an extremely high dose of opioids to avoid withdrawal. Methadone may be more effective for some opioiddependent patients, since they may need higher doses to stave off withdrawal and drug cravings.53,54,61

Buprenorphine is considered to have sufficient agonist properties such that patients routinely describe the medication as allowing them to "feel normal."62

Is It Safe?

Buprenorphine is considered to have a safer profile than full agonists.63 Suboxone, in particular, is considered to have an improved safety profile as compared with methadone or Subutex.2,34

Suboxone has fewer adverse events associated with its use as well as fewer drug-drug interactions among HIV patients on ART than methadone.10 Risk of overdose on buprenorphine is also considered lower than overdose on methadone.58

Worth noting, however, is the potential for overdose when benzodiazepines (i.e., medications used to treat insomnia and anxiety, such as diazepam [Valium] and alprazolam [Xanax], or medications for seizures, such as phenytoin, carbamazepine, and valproic acid) are abused while a patient is taking buprenorphine.64 Risk increases if buprenorphine is taken with large amounts of central nervous system depressants, such as alcohol or benzodiazepines.36

Potential drug-drug interactions also exist between buprenorphine and other sedative drugs, opioid antagonists and agonists, and medications metabolized by the cytochrome P450 3A4 system.53 Additional medications that affect this cytochrome include fluconazole and macrolide antibiotics; and inducers, such as phenobarbital, carbemazepine, phenytoin, and rifampicin.45 (See the Indiana University School of Medicine for a continuously updated list of P450 3A4 drug interactions.)

Interactions between buprenorphine and psychiatric medications have not been studied in humans, except for citalopram (Celexa) and sertraline (Zoloft); neither drug has clinically significant interactions with buprenorphine, so they can be safely coadministered.65

Educating patients about the risk of overdose is imperative. Physicians should ensure patients receive drug screening prior to administration of buprenorphine. (See Polydrug Use and Mental Illness in Chapter 6 for more information.)

How Does Buprenorphine Differ from Methadone?

There are several differences between buprenorphine and methadone, in addition to how and where they are administered. Methadone has been in widespread use for a longer period of time than buprenorphine, so more information is available on long-term safety and treatment outcomes. Since methadone is a full agonist, it is easier for people to overdose because the effects increase with higher doses. Buprenorphine is a partial agonist, so using a larger dose will not heighten the effects of the drug. The propensity for drug-drug interactions with HIV medications is greater with methadone than buprenorphine.

But there are important similarities: Both drugs are known to improve addiction and health-related outcomes, and both are more effective when used in combination with individualized counseling and behavioral therapy, an approach known as medication-assisted treatment, or MAT.

Is Buprenorphine Used for Detox and, if so, How?

Buprenorphine can also be used on an inpatient basis for medically supervised withdrawal (also called “detox”). This helps to reduce opioid withdrawal symptoms and, ultimately, brings the patient into a non-physically dependent state. During medically supervised withdrawal, patients receive buprenorphine daily for up to 10 days; it is discontinued 36 to 48 hours before discharge.

It should be noted, however, that SPNS grantees did not administer buprenorphine in this way. Rather, patients came into SPNS outpatient clinic sites while already in withdrawal and then subsequently received supervised induction of Suboxone.

What Do I Need to Know About Buprenorphine and Liver Enzymes?

Acute viral hepatitis and drug-induced hepatitis can harm the liver, helping to contribute to liver failure and liver disease. Due to the high rates of coinfection with hepatitis C virus (HCV) among those PLWHA who contracted HIV via IDU, routine monitoring of liver enzymes is important. The same is true for patients with previous histories of high alcohol use who may suffer from cirrhosis.9,66,67 (See also “What Are Some Side Effects of Buprenorphine?”)

Though rare, buprenorphine-induced hepatitis is also possible. As such, patients should receive liver enzyme testing at baseline and 1 month post-treatment, as well as quarterly.

Table 1: Buprenorphine and Methadone Comparison

Methadone

Buprenorphine

Method of Administration

Oral; pills, wafers, diskettes, or liquid

Sublingual; tablets or film

Coformulation

No

Yes, available both as monotherapy and in combination with naloxone

Method of Delivery

Through Federally certified Opioid Treatment Programs (OTPs

Through qualified physicians in a primary care setting and OTPs

Dosing Frequency

Daily

Daily; also can be used on alternate days or thrice-weekly

Access

Limited by the number of programs and slots

Limited by the number of patients a physician can treat (100)

Cost

$50 to $300 per week for clinic visits; coverage by public and private payors varies

$4 to $19 per day, depending on dose; coverage by public and private payors for medication and office visits varies

The International Experience

In France, more than 80,000 people have been treated with buprenorphine in their primary care clinic. Buprenorphine treatment within this setting has been shown to destigmatize drug treatment. French studies have shown improved individual, social, and economic benefits, including healthier patients, improved HIV medication adherence, lower viral loads, and better social function.

Buprenorphine treatment was also linked to dramatic decrease in drug overdose, including deaths from drug overdose.

Sources: Kaminski DM. AIDS Community Research Initiative of America. Buprenorphine: the new kid on the block. ACRIA Update. 2005;14(2):22.